Leflunomide Improves Effect of Methotrexate in Active Rheumatoid Arthritis

Laurie Barclay, MD

November 07, 2002

Nov. 7, 2002 — Adding leflunomide to methotrexate was well tolerated and more effective than methotrexate alone in the treatment of active rheumatoid arthritis, according to the results of a randomized, double-blind, placebo-controlled trial reported in the Nov. 5 issue of the Annals of Internal Medicine.

"Disease-modifying antirheumatic drugs may confer greater benefits when combined with the antimetabolite methotrexate," write Joel M. Kremer, MD, from the Center for Rheumatology in Albany, New York, and colleagues.

In this 24-week trial conducted at 20 centers in the U.S. and Canada, 263 patients with rheumatoid arthritis as defined by American College of Rheumatology (ACR) criteria were randomized to treatment with leflunomide or placebo added to existing methotrexate therapy.

At 24 weeks, 20% improvement in ACR criteria occurred in 46.2% of the leflunomide group and 19.5% of the placebo group ( P<.001). Adverse events, which were predominantly mild or moderate, occurred in 89.2% of the leflunomide group and 89.5% of the placebo group. Study discontinuation occurred in 23.1% of patients treated with leflunomide and in 24.8% of patients taking placebo.

The authors recommend hematologic and liver enzyme monitoring, with adjustment of leflunomide dose based on ALT, AST, and serum albumin.

"The combination of two antimetabolic agents, leflunomide and methotrexate, can be used effectively and safely with careful monitoring," the authors write. "It represents a logical alternative for patients who have an incomplete response to monotherapy with maximally tolerated weekly doses of methotrexate."

Aventis Pharmaceuticals supported this study and has financial arrangements with some of its authors.

Ann Intern Med. 2002;137(9):726-733

Reviewed by Gary D. Vogin, MD


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